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- Title
Silencing neurotransmission with membrane-tethered toxins.
- Authors
Auer, Sebastian; Stürzebecher, Annika S.; Jüttner, René; Santos-Torres, Julio; Hanack, Christina; Frahm, Silke; Liehl, Beate; Ibañez-Tallon, Inés
- Abstract
At synaptic terminals, high voltage–activated Cav2.1 and Cav2.2 calcium channels have an essential and joint role in coupling the presynaptic action potential to neurotransmitter release. Here we show that membrane-tethered toxins allowed cell-autonomous blockade of each channel individually or simultaneously in mouse neurons in vivo. We report optimized constitutive, inducible and Cre recombinase–dependent lentiviral vectors encoding fluorescent recombinant toxins, and we also validated the toxin-based strategy in a transgenic mouse model. Toxins delivered by lentiviral vectors selectively inhibited the dopaminergic nigrostriatal pathway, and transgenic mice with targeted expression in nociceptive peripheral neurons displayed long-lasting suppression of chronic pain. Optimized tethered toxins are tools for cell-specific and temporal manipulation of ion channel-mediated activities in vivo, including blockade of neurotransmitter release.
- Subjects
NEURAL transmission; TOXINS; CELL membranes; NEURONS; NEUROTRANSMITTERS
- Publication
Nature Methods, 2010, Vol 7, Issue 3, p229
- ISSN
1548-7091
- Publication type
Article
- DOI
10.1038/nmeth.1425